Debate Over Statins Heats Up as Lipitor Heads Toward a Generic Form

Is a statin the answer to everyone's high cholesterol?

En español | You think of yourself as reasonably healthy, but your doctor has told you that your cholesterol is too high. Should you be taking a cholesterol-lowing drug called a statin to ward off heart disease?

It sounds like a simple question, but getting a straight answer could prove surprisingly elusive.

More than 17 million people have been prescribed Lipitor over the past decade. — Photo by JB Reed/Bloomberg/Getty Images

Doctors usually urge patients to first try to lower their cholesterol by eating better, losing weight and getting more exercise. But lifestyle changes such as those may not be enough, so statins like Lipitor, Crestor, Zocor and Pravachol — proven lifesavers for those who have already suffered a heart attack — are often prescribed for millions of otherwise healthy people with high cholesterol. It's a practice called primary prevention.

Although a large new British study released yesterday seems to indicate that statins are safe for long-term use, some medical experts question whether the practice really saves lives. And they point out that statins, while generally well tolerated, are not without risks.

The debate over statins is bound to intensify in the coming months. The biggest-selling statin — Lipitor, made by Pfizer — which has been prescribed to more than 17 million people and made more than $100 billion in sales over the past decade, is scheduled to come off patent Nov. 30. Over the next year prices are expected to drop gradually as generic forms of Lipitor become available, which could encourage many more people to use them.

In fact, Crestor at about $5 a pill, soon will be the only remaining statin still under patent. But even if you take cost out of the picture, says Mark Hlatky, M.D., a cardiologist and professor at Stanford University School of Medicine, "you could still have questions about" the use of statins.

"The first question is, 'Does it work and how do the risks and benefits balance out for individual people?' " he says.

Dangers of high doses

That question was highlighted in June, when the Food and Drug Administration (FDA) warned that no new patients should start taking an 80 mg dose of simvastatin — the generic name for Zocor — because it carries a higher risk of serious muscle damage that could lead to kidney failure and death. Meanwhile, a review of five major drug trials showed that high-dose statin users were slightly more likely to develop diabetes than those on a lower dose.

Still, many researchers see statins, which have other effects besides lowering cholesterol, as miracle drugs. Intriguing studies have linked statins to a lower risk of colorectal cancer, rheumatoid arthritis, cataracts and multiple sclerosis. Statin users see fewer kidney complications after serious surgery and have better recovery from brain injury. They also are 60 percent less likely to develop high-grade prostate cancer. Overall, their risk of dying is reduced, largely because of fewer deaths from infection and respiratory illness.

A set of guidelines issued by the National Heart, Lung and Blood Institute (NHLBI) helps doctors decide when to prescribe statins, which provide much of their benefit by lowering LDL, the so-called "bad" cholesterol, Hlatky says.

They factor in LDL levels, signs of coronary disease and risk factors such as smoking, diabetes, high blood pressure and too little HDL, the "good" cholesterol. They also use a risk calculator — based on the findings of the huge, multigenerational Framingham Heart Study — to calculate a patient's likelihood of dying from heart disease within the next 10 years.

Statins should be considered for patients with elevated LDL, two or more risk factors and a heightened 10-year risk of dying, the guidelines say.

Many practitioners, however, say the NHLBI guidelines don't go far enough, in light of recent studies suggesting that an even wider range of people might benefit from taking statins.

A landmark clinical study dubbed JUPITER ("Justification for the Use of Statins in Primary Prevention"), followed 17,802 men and women with normal cholesterol but with high levels of C-reactive protein, a sign of inflammation associated with greater risk for heart disease. (That protein is measured in a blood test.)

The trial was halted early because those taking placebos seemed to be at a higher risk for death. Lead author Paul Ridker, Harvard Medical School professor and director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital, says the men and women taking statins saw 45 percent fewer heart attacks and strokes than those on placebos, along with a 20 percent reduction in deaths.

But the study has some vociferous critics, who believe statins are overprescribed and think that the risks and expense of taking the drugs outweigh any possible benefit in primary prevention.

Statins don't cut the risk of dying nearly as much as heart-healthy habits do, contends John Abramson, M.D., a lecturer with the Department of Health Care Policy at Harvard Medical School.

"The healthy lifestyle includes regular exercise, a Mediterranean-style diet, not smoking and drinking in moderation," he says. "People who do that seem to have about a 60 percent lower death rate than people who don't." The United States lags behind other countries in heart health measures despite our high rate of statin use, Abramson observes. "The bottom line is, most of your health is in your own hands," he says. "Don't let other people convince you that they can fix it with other products."

Today nearly 32 million Americans — one in four Americans age 45 and older — take statins, according to the National Center for Health Statistics.

A lifetime of medication

Stanford's Hlatky says his concern about the JUPITER trial it that it only ran for about two years.

"Most people are not going to take the drug for two years and stop," he says. "They're going to take it for the rest of their natural lives." Statins can occasionally cause liver problems or a muscle-destroying condition called rhabdomyolysis, he points out. As the recent findings about the diabetes risk reveals, no one knows whether there might be other side effects after taking the drugs for 10 or 20 years.

Today nearly 32 million Americans — one in four Americans age 45 and older — take statins.

Hlatky says brand-new results from Britain's Heart Protection Study are "reassuring," because an 11-year follow-up of 20,536 patients found statin users were not at increased risk for cancer or death compared with those taking a placebo. They were also 23 percent less likely to have suffered a major heart-related event.

Stay tuned

An expert panel is currently updating the guidelines, says Michael Blaha, M.D., a research and clinical fellow at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. And, he says, "without a doubt" they're going to expand the number of people who should be on statins.

He supports the idea of using statins to prevent heart disease. If you wait until you've had your first heart attack, he asks, "haven't you waited too long?"